Some facts:
-after immunization, female rats produce more antibody and more vigorous T-cell activation that male mice (human data contradicting).
-women have higher CD4+ lymphocytes than men.
-higher production of Th1 cytokines in women.
-cytokine production is enhanced in vitro in the presence of estrogen.
Studies have focused mainly on the following sex hormones: estrogen, progesterone, and testosterone. Along these lines, there huge increase in estrogen and progesterone production during 3rd trimester of pregnancy. In MS and RA, disease activity decreases during pregnancy but moreso during the 3rd trimester. There is then a post-pardum "flare" that is often seen when estrogen and progesterone levels fall. These hormones could alter the balance of Th responses, with estrogen and progesterone pushing towards more Th2.
Overall, there appear to be major differences between male and female immune systems, and these differences influence the frequency of autoimmunity in females greater than males. There seems to be an effect from sex hormones, but genetic differences are likely as well. Perhaps lifestyle differences between genders could also affect immune system function? Understanding the link between sex differences in immunity and autoimmunity will provide novel insight into how we think about these diseases and how we prevent and treat them.
So given the fact that autoimmune diseases are in remision during pregnancy, I would think that Tregs are primarily responsible for that. In class I remember we talked about why you are not essentially allergic to your baby, and don't essentially reject your child, has to do with a Treg mediated response. There probably is some kind of mechanism involving estrogen and progesterone levels in Treg/IL-10/TGF-B regulation. Here is kind of a random thought, birth control essentially tricks your body into thinking you are pregnant, so having said that, wouldn't autoimmune disorder flare ups decrease while on birth control? How would autoimmune symptoms change throughout the estrogen cycle?
ReplyDeleteI did some research on how estrogen effects immune system and found an interesting paper that links it to estrogen regulation of nitric oxide (NO). Inducible nitric oxide synthase (iNOS) catalyzes the conversion of L-arginine to citrulline and NO. Macrophages and other phagocytic cells express iNOS. Production of iNOS is simulated by IFNs and APC, which leads to production of NO. NO modulates production of TNFa and IL-6, thus increasing activity of phagocytes against pathogens. Studies showed when estrogen concentration is low, iNOS is induced and vice versa. That could be an explanation why female immune system is stronger, although more prone to autoimmune diseases.
ReplyDeleteReference:
Daniela Verthelyi. Female’s Heightened Immune Status: Estrogen, T Cells, and Inducible Nitric Oxide Synthase in the Balance. Endocrinology. 2006
Just and interesting side note...
ReplyDeleteStress research has also shown that women are much more reactive (biologically) to stressors.
When you look at the immunologic literature, women are known to have different patterns and degrees of immune response than men.
Genetically, the male Y chromosome has less DNA than the corresponding female X chromosome.
Although immune function is certainly multifactorial in nature, one has to wonder if there is a common underlying mechanism to explain the multiple differences noted between men and women across immunology, stress physiology, and genetics.
Continuing the chromosome talk. Last year National Jewish found a B-cell subset that they believe could be part of the cause for women having a higher degree of autoimmune disorders than men. They had a mouse model which looked at healthy aged female mice, and found an increase in this particular B-cell group. They found that if you remove the B-cells the amount of auto antibody in the system is diminished. Very interesting stuff.
ReplyDeletehttp://www.nationaljewish.org/about/mediacenter/pressreleases/2011/cd11c/